KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification

Nat Commun. 2016 Oct 31;7:13227. doi: 10.1038/ncomms13227.


Lysine acetylation is a widespread post-translational modification regulating various biological processes. To characterize cellular functions of the human lysine acetyltransferases KAT2A (GCN5) and KAT2B (PCAF), we determined their acetylome by shotgun proteomics. One of the newly identified KAT2A/2B substrate is polo-like kinase 4 (PLK4), a key regulator of centrosome duplication. We demonstrate that KAT2A/2B acetylate the PLK4 kinase domain on residues K45 and K46. Molecular dynamics modelling suggests that K45/K46 acetylation impairs kinase activity by shifting the kinase to an inactive conformation. Accordingly, PLK4 activity is reduced upon in vitro acetylation of its kinase domain. Moreover, the overexpression of the PLK4 K45R/K46R mutant in cells does not lead to centrosome overamplification, as observed with wild-type PLK4. We also find that impairing KAT2A/2B-acetyltransferase activity results in diminished phosphorylation of PLK4 and in excess centrosome numbers in cells. Overall, our study identifies the global human KAT2A/2B acetylome and uncovers that KAT2A/2B acetylation of PLK4 prevents centrosome amplification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation*
  • Amino Acid Motifs
  • Animals
  • Cell Cycle / physiology
  • Centrioles / metabolism
  • Centrosome / metabolism*
  • Centrosome / ultrastructure
  • Drosophila melanogaster
  • HEK293 Cells
  • HeLa Cells
  • Histone Acetyltransferases / metabolism*
  • Histones / chemistry
  • Humans
  • Lysine / chemistry
  • Mice
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Phosphorylation
  • Plasmids / metabolism
  • Point Mutation
  • Protein Domains
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Spindle Apparatus / metabolism
  • p300-CBP Transcription Factors / metabolism*


  • Histones
  • RNA, Small Interfering
  • Histone Acetyltransferases
  • KAT2A protein, human
  • KAT2B protein, human
  • p300-CBP Transcription Factors
  • PLK4 protein, human
  • Protein Serine-Threonine Kinases
  • Lysine